Biodistribution of [⁶⁴Cu]Cu²⁺ and variance of metallothionein during tumor treatment by copper

The kinetic distribution patterns of [⁶⁴Cu]Cu²⁺ in normal mice and in mice bearing tumors (HepA, ascitic tumor) after i.v. injection were similar. The i.v. injected [⁶⁴Cu]Cu²⁺ concentrated into mouse liver first and then went to other organs and tissues, such as kidney and tumor. Most of the [⁶⁴Cu]Cu²⁺ injected concentrated into the liver within 4 h, and about 8% of the total [⁶⁴Cu]Cu²⁺ injected concentrated into the tumor cells at 24 h after i.v. injection. About 80% and 90% of the soluble [⁶⁴Cu]Cu in the livers of tumor-bearing mice and normal mice, respectively, existed as [⁶⁴Cu]CuMT (metallothionein [MT] is a small protein with many cysteine residues) at 4 h after i.v. injection, while about 43% of the soluble [⁶⁴Cu]Cu²⁺ in tumor cells combined with MT at 6 h after i.v. injection. After 10 days oral administration of 150 μg/g body weight copper acetate, the concentration of MT in tumor cells reduced sharply, from 316 μg/g tissue to 152 μg/g tissue, while it increased slightly, from 375 μg/g tissue to 439 μg/g tissue, in the livers of tumor-bearing mice (HepA, solid tumor). The results suggest that MT contributes to the metabolism of copper that is localized mainly in the liver after copper administration and that copper can concentrate into mouse tumor cells followed by the reduction of MT in tumor cells.